Catalytic asymmetric methods for organic synthesis provide access to single enantiomers of three-dimensional chiral molecules that serve as the basis of new medicines, materials and catalysts. Csp2—Csp2 cross-coupling reactions between arylboronic acid and aryl halides are widely used in both academia and industry and are strategically important in the development of new agrochemicals and pharmaceuticals.
One of the most widely used approaches to carbon-carbon bond formation in the fine chemical, pharmaceutical, and agrochemical industries, as well as in the synthesis of organic materials, is sp2-sp2 cross-coupling1. In particular the Suzuki-Miyaura reaction (see Scheme 1) is robust, convenient and widely used in the synthesis of lead compounds for the development of new medicines as it is well-suited to producing libraries of compounds2-4.

The development of robust and widely applicable methods that form single enantiomer chiral products is a major contemporary research goal5. Hayashi developed rhodium-catalyzed asymmetric conjugate addition reactions of boronic acid nucleophiles to prochiral α,β-unsaturated ketones with excellent yield and enantioselectivity6,7 (see Scheme 2) and many related protocols have since been developed8.

Evans reported that alkylations with stabilized nucleophiles9,10 and arylations with non-stabilized aryl zinc nucleophiles11 are highly stereospecific processes; overall retention of configuration is observed using stabilized nucleophiles and overall inversion occurs with arylzinc compounds, so that highly enantiomerically enriched compounds can be obtained by starting from single enantiomer allylic coupling partners (see Scheme 3).

A particularly powerful class of asymmetric allylic alkylation (AAA) reactions allow the conversion of racemic starting materials into single enantiomer products12,13 rather than starting from single enantiomer or prochiral starting materials. Pd-catalyzed processes that convert a racemic mixture of starting materials into a new single enantiomer product are commonly referred to as dynamic kinetic asymmetric transformations (DYKATs) as originally developed by Trost (see Scheme 4). DYKATs can now be used with a wide variety of stabilized nucleophiles and an array of metal catalysts14 and several non-stabilized sp3-hybridized nucleophiles can now be used in certain related procedures15-18.

In spite of the advancements discussed above, there remains a need for alternative or more effective means of realising asymmetric allylic addition reactions.
The present invention was devised with the foregoing in mind.